May 08, 2012
Individual Cancer Cells Examined For Mutations

Multiple blood borne cancer cells from the same person examined individually are genetically heterogeneous.

STANFORD, Calif. The cells that slough off from a cancerous tumor into the bloodstream are a genetically diverse bunch, Stanford University School of Medicine researchers have found. Some have genes turned on that give them the potential to lodge themselves in new places, helping a cancer spread between organs. Others have completely different patterns of gene expression and might be more benign, or less likely to survive in a new tissue. Some cells may even express genes that could predict their response to a specific therapy. Even within one patient, the tumor cells that make it into circulating blood vary drastically.

The finding underscores how multiple types of treatment may be required to cure what appears outwardly as a single type of cancer, the researchers say. And it hints that the current cell-line models of human cancers, which showed patterns that differed from the tumor cells shed from human patients, need to be improved upon.

The new study, which will be published online May 7 in PLoS ONE, is the first to look at so-called circulating tumor cells one by one, rather than taking the average of many of the cells. And it's the first to show the extent of the genetic differences between such cells.

I do not find this at all surprising. A tumor has large numbers cells undergoing rapid division and more mutations happen in each cell division. Many of those cancer cells are sick and dying, making room for cells with mutations that provide advantages for spreading. Natural selection operates very strongly for cancer cells which secrete more angiogenesis factors to promote blood vessel growth needed for tumor growth, which secrete factors that dampen immune response against them, and which have greater ability to move around in the blood stream and land in other parts of the body and divide. So a tumor becomes genetically very diverse.

What's more interesting: the tools used to do the study. Those tools will some day help to identify all the important genetic subpopulations of cancer cells in each cancer patient.

First the researchers used a technology they developed to separate the literally 1-in-a-million circulating tumor cells (CTCs) from normal blood cells.

To make their latest discovery, Jeffrey, along with an interdisciplinary team of engineers, quantitative biologists, genome scientists and clinicians, relied on a technology they developed in 2008. Called the MagSweeper, it's a device that lets them isolate live CTCs with very high purity from patient blood samples, based on the presence of a particular protein EpCAM that's on the surface of cancer cells but not healthy blood cells.

Then they used microfluidic chips to look at each individual cancer cells.

So once Jeffrey and her collaborators isolated CTCs using the MagSweeper, they turned to a different kind of technology: real-time PCR microfluidic chips, invented by a Stanford collaborator, Stephen Quake, PhD, professor of bioengineering. They purified genetic material from each CTC and used the high-throughput technology to measure the levels of all 95 genes at once. The results on the cell-line-derived cells were a success; the genes in the CTCs reflected the known properties of the mouse cell-line models. So the team moved on to testing the 95 genes in CTCs from 50 human breast cancer patients 30 with cancer that had spread to other organs, 20 with only primary breast tumors.

To defeat cancer we need cheap and highly powerful microfluidic devices to identify every trick each cancer is using to survive and spread. While in this study only at most 5 individual CTCs were analyzed in the future costs will drop. Cheaper microfluidic devices will enable analysis of many more CTCs per patient yielding more detailed analyses.

Next we need microfluidic devices that can construct agents (e.g. gene therapies, antibodies, specialized immune cells) that will target each of the cancer subpopulations.

Even better: Imagine early stage cancer detection by periodic blood tests fed into very microfluidic devices installed in a fully automated home medical test lab. Earlier stage discovery brings the advantage that the cancer hasn't yet mutated adaptations for metastasis.

Share |      Randall Parker, 2012 May 08 10:59 PM  Biotech Cancer

PacRim Jim said at May 9, 2012 1:45 AM:

Start saving your money.
Personalized medicine will be almost as expensive as it will be effective.
The golden years, indeed.

Lono said at May 9, 2012 9:38 AM:

Impressive! - We are so close now to becoming masters of our own biological destiny.

If only we could do a better job prioritizing our real enemies.

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